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@ARTICLE{Weigand:132949,
author = {T. Weigand and B. Singler and T. Fleming and P. Nawroth and
K. Klika$^*$ and C. Thiel and H. Baelde and S. F. Garbade
and A. H. Wagner and M. Hecker and B. A. Yard and A.
Amberger and J. Zschocke and C. P. Schmitt and V. Peters},
title = {{C}arnosine {C}atalyzes the {F}ormation of the
{O}ligo/{P}olymeric {P}roducts of {M}ethylglyoxal.},
journal = {Cellular physiology and biochemistry},
volume = {46},
number = {2},
issn = {1421-9778},
address = {Basel},
publisher = {Karger},
reportid = {DKFZ-2018-00588},
pages = {713 - 726},
year = {2018},
abstract = {Reactive dicarbonyl compounds, such as methylglyoxal (MG),
contribute to diabetic complications. MG-scavenging
capacities of carnosine and anserine, which have been shown
to mitigate diabetic nephropathy, were evaluated in vitro
and in vivo.MG-induced cell toxicity was characterized by
MTT and MG-H1-formation, scavenging abilities by Western
Blot and NMR spectroscopies, cellular carnosine transport by
qPCR and microplate luminescence and carnosine concentration
by HPLC.In vitro, carnosine and anserine dose-dependently
reduced N-carboxyethyl lysine (CEL) and advanced glycation
end products (AGEs) formation. NMR studies revealed the
formation of oligo/polymeric products of MG catalyzed by
carnosine or anserine. MG toxicity (0.3-1 mM) was
dose-dependent for podocytes, tubular and mesangial cells
whereas low MG levels (0.2 mM) resulted in increased cell
viability in podocytes $(143±13\%,$ p<0.001) and tubular
cells $(129±3\%,$ p<0.001). Incubation with
carnosine/anserine did not reduce MG-induced toxicity,
independent of incubation times and across large ranges of
MG to carnosine/anserine ratios. Cellular carnosine uptake
was low $(<0.1\%$ in 20 hours) and cellular carnosine
concentrations remained unaffected. The putative carnosine
transporter PHT1 along with the taurine transporter (TauT)
was expressed in all cell types while PEPT1, PEPT2 and PHT2,
also belonging to the proton-coupled oligopeptide
transporter (POT) family, were only expressed in tubular
cells.While carnosine and anserine catalyze the formation of
MG oligo/polymers, the molar ratios required for protection
from MG-induced cellular toxicity are not achievable in
renal cells. The effect of carnosine in vivo, to mitigate
diabetic nephropathy may therefore be independent upon its
ability to scavenge MG and/or carnosine is mainly acting
extracellularly.},
cin = {G404},
ddc = {540},
cid = {I:(DE-He78)G404-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29621776},
doi = {10.1159/000488727},
url = {https://inrepo02.dkfz.de/record/132949},
}